Microneedle Formulation for Treating Cognitive Impairment in Patients at-risk for Alzheimer's Disease Related Dementia (ADRD) and Vascular Contributions to Cognitive Impairment and Dementia (VCID)

The purpose of this request for an administrative supplement is to add an additional dose to the PK swine studiesas recommended by the reviewers articulated in our originalSummary StatementAfter further analysiswe concur with Reviewers suggestion of adding an extra doseespecially considering the change in formulation of using a new glycosylated peptide which may have different dosing PKWe believe this modification will increase the overall impact of the project consistent with its originally approved objectives and purposes by enabling a more robustdose comparison of the PK parameters of the hMTS device and thepeptidesSpecificallywe will repeat Objectiveas described in the parent study with amg doseAll other experimental parameters will remain the sameThe inclusion of and dose was unanticipated when writing the original applicationand the supplement is within scope of the parent awardIn older adultsinflammatory related diseasessuch as cardiac disease or heart failure that lead to decreased brain perfusion and increased brain and systemic inflammationare known to increase the risk for dementia and the development of ADRD and VCIDProNeurogen has been working with our University of Arizona collaborators to develop novel AngiotensinAngformulations to treat inflammation related cognitive impairment in heart disease patients at for risk ADRD and VCIDThese novel peptide formulations are designed to act on Mas receptorsMasRwithin the brain vascular endothelium and neuronal cells to decrease brain ROS productionneuroinflammation and improve cerebral vascular blood flowWe have begun to translate these preclinical findings into novel peptide therapeutics to treat inflammation related cognitive impairment in patients with heart disease who are at risk for ADRD or VCIDWe have an approved FDA INDand support for Phasea trials for native Angfor treatment of cognitive impairment in heart failureHFpatients and NIH support for our trial in cardiac bypass surgery patientsCABGWe are currently enrolling in these studiesOur current approved treatment protocol is once a daysubcutaneousmicrog kg injection using a standard needle and syringe fordays in our HF patientsHoweverin order to increase patient compliance and comfort with injections as well as accelerate commercialization we are currently investigating new formulations and injection methods that are more patient friendly and easier to administerThe goal of the present Phase I project is to begin development of a microneedle injection platform for the administration of our novel peptide therapies for treating brain inflammation related cognitive impairmentWe will begin feasibility studies with theM Drug Delivery Systems to develop a microneedle injection platform for our AngpeptidesObjectiveComplete a PK study following administration of amg dose of Angpeptides comparingM hMTS to subcutaneous injections in swine PROJECT NARRATIVE Our vision is to advance our novel Angiotensinpeptides as a first in class therapy to reduce inflammatorydisease related cognitive impairment in patients at risk for Alzheimer s Disease and Related DementiasADRDand Vascular Contributions to Cognitive Impairment and DementiaVCIDThe goal of the present Phase I project is to begin development of a microneedle injection platform for the administration of our novel peptide therapies for treating brain inflammation related cognitive impairment